The present invention relates to the use of debranched starch in the preparation of pharmaceutical pellets by extrusion-spheronization.
Extrusion-spheronization is a process well-known in the art of pharmaceuticals, to prepare spheres for pharmaceutical uses, including both conventional and controlled release dosage forms. The process is based on the following steps:                a) mixing at least one debranched starch and a liquid to form a moistened plastically deformable mass;        b) extruding the mass to obtain an extrudate;        c) spheronizing the extrudate to obtain a plurality of substantially spherical pellets; and        d) drying of the pellets.        
Such dosage forms may also optionally consist of several inert materials, referred to as excipients, in addition to the active ingredient, which is present in amounts sufficient to accomplish the desired pharmaceutical effect. These excipients are generally classified according to their functions, such as fillers (also called bulking agents and diluents), binders which hold the ingredients together, binder-fillers which perform both functions and disintegrants which help the dosage form to break apart and release the active ingredient when placed in a fluid environment.
Conventionally, extrusion-spheronization uses microcrystalline cellulose as the primary pharmaceutical excipient. However, microcrystalline cellulose is expensive and also is inadequate for use with certain active ingredients. Furthermore, since microcrystalline cellulose-based pellets do not disintegrate in gastrointestinal fluids, the release of less soluble active ingredients is prolonged. Due to these limitations, there is a need for microcrystalline cellulose replacement for use in pellet production.
Alternative excipients have been tried in the art, primarily cellulose derivatives, as well as blends. However, it has been difficult to find a replacement for microcrystalline cellulose as the primary excipient in extrusion-spheronization. Many of the alternatives tried have failed in such regards as difficult to extrude or spheronize, poor water absorption or retention within the extrudate, low quality size and shape distribution, and/or poor dissolution and release of the active agent.
Corn starch, wheat starch and waxy corn starch have been tried in extrusion-spheronization and determined to be unsatisfactory due to inadequate consistency and the fact that water is not homogeneously distributed, resulting in poor spheronization and inadequate pellets.
Surprisingly, it has now been discovered that crystalline, debranched starches provide an excellent replacement for microcrystalline cellulose in extrusion spheronization, and have excellent characteristics and properties.